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Review
. 2020 Jul 27;9(8):452.
doi: 10.3390/antibiotics9080452.

The Desotamide Family of Antibiotics

Asif Fazal  1   2 , Michael E Webb  2 , Ryan F Seipke  1
Affiliations
Review

The Desotamide Family of Antibiotics

Asif Fazal et al. Antibiotics (Basel). .

Abstract

Microbial natural products underpin the majority of antimicrobial compounds in clinical use and the discovery of new effective antibacterial treatments is urgently required to combat growing antimicrobial resistance. Non-ribosomal peptides are a major class of natural products to which many notable antibiotics belong. Recently, a new family of non-ribosomal peptide antibiotics were discovered-the desotamide family. The desotamide family consists of desotamide, wollamide, surugamide, ulleungmycin and noursamycin/curacomycin, which are cyclic peptides ranging in size between six and ten amino acids in length. Their biosynthesis has attracted significant attention because their highly functionalised scaffolds are cyclised by a recently identified standalone cyclase. Here, we provide a concise review of the desotamide family of antibiotics with an emphasis on their biosynthesis.

Keywords: NRPS; cyclases; natural products; non-ribosomal peptides; standalone enzymes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The desotamide family of antibiotics. Numbering indicates the amino acid position within the macrocycle. Red coloured text indicates biosynthetic precursors discussed in Section 4. NFK = N-formyl-kynurenine, Kyn = kynurenine, AMPA = 3-amino-2-methylpropionic acid.
Figure 2
Figure 2
Biosynthetic gene clusters (BGCs) of the desotamide family of antibiotics. BGCs are drawn to relative scale. Colour-coding denotes deduced functionality of gene products. dsa = desotamide, sur = surugamide, ulm = ulleungmycin, nsm = noursamycin, cur = curacomycin.
Figure 3
Figure 3
Biosynthetic pathways of the desotamide family of antibiotics. Red colouring denotes biosynthetic precursors discussed in Section 4. A = adenylation domain, PCP = peptidyl carrier protein, C = condensation, E = epimerase. The biosynthesis of desotamide A, ulleungmycin A, noursamycin B or curacomycin, surugamide A and surugamide F is shown.
Figure 4
Figure 4
SurE-mediated offloading/cyclisation of surugamide A (left) and surugamide F (right) from the terminal biosynthetic modules of SurD and SurC, respectively.
See this image and copyright information in PMC

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